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Despite its prevalence, approximately one\u2010third of patients do not benefit sufficiently from available treatments, and few new drugs have been developed recently. Consequently, more efficient methods are needed to evaluate a broader range of treatment options quickly. Platform trials offer a promising solution, as they allow for the assessment of multiple investigational treatments simultaneously by sharing control groups and by reducing both trial activation and patient recruitment times. The objective of this simulation study was to support the design and optimisation of a phase II superiority platform trial for MDD, considering the disease\u2010specific characteristics. In particular, we assessed the efficiency of platform trials compared to traditional two\u2010arm trials by investigating key design elements, including allocation and randomisation strategies, as well as per\u2010treatment arm sample sizes and interim futility analyses. Through extensive simulations, we refined these design components and evaluated their impact on trial performance. The results demonstrated that platform trials not only enhance efficiency but also achieve higher statistical power in evaluating individual treatments compared to conventional trials. The efficiency of platform trials is particularly prominent when interim futility analyses are performed to eliminate treatments that have either no or a negligible treatment effect early. Overall, this work provides valuable insights into the design of platform trials in the superiority setting and underscores their potential to accelerate therapy development in MDD and other therapeutic areas, providing a flexible and powerful alternative to traditional trial designs.<\/jats:p>","DOI":"10.1002\/pst.70025","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T16:04:41Z","timestamp":1756310681000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Design Considerations for a Phase <scp>II<\/scp> Platform Trial in Major Depressive Disorder"],"prefix":"10.1002","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0924-1277","authenticated-orcid":false,"given":"Michaela Maria","family":"Freitag","sequence":"first","affiliation":[{"name":"Institute of Biometry and Clinical Epidemiology Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t zu Berlin, and Berlin Institute of Health  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9218-6919","authenticated-orcid":false,"given":"Dario","family":"Zocholl","sequence":"additional","affiliation":[{"name":"Institute of Biometry and Clinical Epidemiology Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t zu Berlin, and Berlin Institute of Health  Berlin Germany"},{"name":"Institute for Medical Biometry, Informatics and Epidemiology Faculty of Medicine, University of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5398-6334","authenticated-orcid":false,"given":"Elias Laurin","family":"Meyer","sequence":"additional","affiliation":[{"name":"Center for Medical Data Science, Medical University of Vienna  Vienna Austria"},{"name":"Berry Consultants  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5188-4799","authenticated-orcid":false,"given":"Stefan M.","family":"Gold","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t zu Berlin, and Berlin Institute of Health  Berlin Germany"},{"name":"Medical Department, Section Psychosomatics Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t zu Berlin, and Berlin Institute of Health  Berlin Germany"},{"name":"DZPG, German Center for Mental Health  Berlin Germany"},{"name":"INIMS, Universit\u00e4tsklinikum Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4400-7541","authenticated-orcid":false,"given":"Marta Bofill","family":"Roig","sequence":"additional","affiliation":[{"name":"Center for Medical Data Science, Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"De Smedt","sequence":"additional","affiliation":[{"name":"Johnson &amp; 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